Specific 17β-thiobenzoyl-4-aza-5α-androst-1-en-3-ones as antiandrogen agents

Abstract

Specific 17β-thiobenzoyl-4-aza-5α-androst-1-en-3-ones as antiandrogenic agents of the formula: ##STR1## wherein R is selected from hydrogen, methyl and ethyl and R 2 is phenyl substituted with one or more of: --SH, --SC 1 --C 4 alkyl, --SO--C 1 --C 4 alkyl, --SO 2 --C 1 --C 4 alkyl, --SO 2 N--(C 1 -C 4 alkyl) 2 , C 1 -C 4 alkyl, --(CH 2 ) m SH, --S(CH 2 ) n OCOCH 3 , where m is 1-4, n is 1-3, and providing C 1 -C 4 alkyl is only present when one of the above sulfur-containing radicals is present, wherein the dotted line can represent a double bond, and pharmaceutically acceptable esters and salts thereof. Also included is a pharmaceutical formulation thereof. The above compounds are active as antiandrogenic agents and thus are useful topically for treatment of acne, seborrhea, female hirsutism, and systemically in treatment of benign prostatic hypertrophy.

What is claimed is: 
     
       1. A compound of formula: ##STR7## wherein R is selected from hydrogen, methyl and ethyl and R 2  is phenyl substituted with one or more of: --SC 1  -C 4  alkyl, --SOC 1  -C 4  alkyl, --SO 2  C 1  -C 4  alkyl, --SO 2  N(C 1  -C 4  - alkyl) 2 , C 1  -C 4  alkyl, --(CH 2 ) m  SH, --S--(CH 2 ) n  --O--COCH 3 , where m is 1-4, n is 1-3, providing C 1  -C 4  alkyl is only present when one of the above sulfur-containing radicals is present, wherein the dotted line can represent a double bond, and pharmaceutically acceptable esters and salts thereof.   
     
     
       2. The compound of claim 1 wherein: R is hydrogen, methyl or ethyl and   R 2  is methylthiophenyl, methylsulfinyl-phenyl, methylsulfophenyl, aminosulfophenyl, thioethylphenyl or acetoxymethylthiophenyl.   
     
     
       3. The compound of claim 1 which is a member selected from the group: 17β-(4-methylthiophenylcarbonyl)-4-aza-5α-androst-1-en-3-one;   17β-(4-methylsulfinylphenylcarbonyl)-4-aza-5α-androst-1-en-3-one;   17β-(4-methylsulfophenylcarbonyl)-4-aza-5α-androst-1-en-3-one;   17β-(3-methylsulfinylphenylcarbonyl)-4-aza-5α-androst-1-en-3-one;   17β-(4-N,N-dimethylaminosulfophenylcarbonyl)-4-aza-5α-androst-1-en-3-one;   17β-(2-ethyl-4-methylthiophenylcarbonyl)-4-aza-5α-androst-1-en-3-one;   17β-(4-thioethylphenylcarbonyl)-4-aza-5α-androst-1-en-3-one;   17β-(4-acetoxymethylthiophenylcarbonyl)-4-aza-4-methyl-5α-androst-1-en-3-one;   1β -(2-methyl-4-methylthiophenylcarbonyl)-4-aza-4-methyl-5α-androst-1-en-3-one;   17β-(2-methyl-4-methylsulfinylphenylcarbonyl)-4-aza-4-methyl-5α-androst-1-en-3-one;   17β-(2-isopropyl-4-methylsulfophenylcarbonyl)-4-aza-4-methyl-5α-androst-1-en-3-one;   17β-(4-methylthiophenylcarbonyl)-4-aza-4-methyl-5α-androstan-3-one;   17β-(4-methylsulfinylphenylcarbonyl)-4-aza-4-methyl-5α-androstan-3-one; or   17β-(4-methylsulfophenylcarbonyl)-4-aza-4-methyl-5α-androstan-3-one.   
     
     
       4. A method of treating the hyperandrogenic condition of acne vulgaris, seborrhea, female hirsutism, and benign prostatic hypertrophy comprising parenteral administration to a patient in need of such treatment of a therapeutically effective amount of a compound of formula: ##STR8## wherein R is selected from hydrogen, methyl and ethyl, and R 2  is phenyl substituted with one or more of: --SC 1  -C 4  alkyl, --SOC 1  -C 4  alkyl, --SO 2  C 1  -C 4  alkyl, --SO 2  N(C 1  -C 4  -alkyl) 2 , C 1  -C 4  alkyl, --(CH 2 ) m  SH, --S--(CH 2 ) n  --OCOCH 3 , where m is 1-4, n is 1-3, providing C 1  -C 4  alkyl is only present when one of the above sulfur-containing radicals is present, wherein the dotted line can represent a double bond, and pharmaceutically acceptable esters and salts thereof.   
     
     
       5. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound according to claim 1. 
     
     
       6. A compound of the formula: ##STR9## wherein R is selected from hydrogen, methyl and ethyl, and R 2  is phenyl substituted with one or more of: --SC 1  -C 4  alkyl, --SOC 1  -C 4  alkyl, --SO 2  C 1  -C 4  alkyl, --SO 2  N(C 1  -C 4  -alkyl) 2 , C 1  -C 4  alkyl, --(CH 2 ) m  SH, --S--(CH 2 ) n  --OCOCH 3 , where m is 1-4, n is 1-3, and providing C 1  -C 4  alkyl is only present when one of the above sulfur-containing radicals is present, wherein the dotted line can represent a double bond, and pharmaceutically acceptable esters and salts thereof.